Understanding the impact of tuberous sclerosis complex: development and validation of the TSC-PROM

Abstract

Background Tuberous sclerosis complex (TSC) is a rare and complex genetic disorder, associated with tumor growth in various organ systems, epilepsy, and a range of neuropsychiatric manifestations including intellectual disability. With improving patient-centered care and targeted therapies, patient-reported outcome measures (PROMs) are needed to measure the impact of TSC manifestations on daily functioning. The aim of this study was to develop a TSC-specific PROM for adults that captures the impact of TSC on physical functions, mental functions, activity and participation, and the social support individuals with TSC receive, called the TSC-PROM. Methods COSMIN methodology was used to develop a self-reported and proxy-reported version. Development and validation consisted of the following studies: PROM development, content validity, structural validity, internal consistency, and construct validity. The International Classification of Functioning and Disability was used as a framework. Content validity was examined by a multidisciplinary expert group and cognitive interview study. Structural and construct validity, and internal consistency were examined in a large cohort, using confirmatory factor analysis, hypotheses testing, and Cronbach’s alpha. Results The study resulted in an 82-item self version and 75-item proxy version of the TSC-PROM with four subscales (physical functions 18 and 19 items, mental functions 37 and 28 items, activities and participation 13 and 14 items, social support 13 items, for self version and proxy version respectively). Sufficient results were found for structural validity with sufficient unidimensionality for each subscale. With regard to construct validity, 82% of the hypotheses were met for the self version and 59% for the proxy version. The PROM showed good internal consistency (Cronbach’s alpha 0.78–0.97). Conclusions We developed a PROM for adults with TSC, named TSC-PROM, showing sufficient evidence for reliability and validity that can be used in clinical and research settings to systematically gain insight into their experiences. It is the first PROM in TSC that addresses the impact of specific TSC manifestations on functioning, providing a valuable, patient-centered addition to the current clinical outcomes.

Identification of hub genes significantly linked to tuberous sclerosis related-epilepsy and lipid metabolism via bioinformatics analysis

“…Tuberous sclerosis complex (TSC) is a rare autosomal dominant genetic disorder characterized by the growth of benign tumors in multiple organ systems, including the skin, kidneys, lungs, heart, and brain. A common feature of TSC is epilepsy ( 1 ). Epileptic seizures are a progressively worsening and dynamic process in which several cellular, molecular and pathophysiological mechanisms may be involved, including mammalian target of rapamycin (mTOR) dysregulation and synaptic abnormalities ( 2 ).…”

Correction: Understanding the impact of tuberous sclerosis complex: development and validation of the TSC-PROM

“…The original article [ 1 ] contained typographical errors in Additional Files 2 and 3 which have since been amended.…”